Causal effects of sleep traits on metabolic syndrome and its components: a Mendelian randomization study.

PURPOSE: Previous observational studies have suggested an association between sleep disturbance and metabolic syndrome (MetS). However, it remains unclear whether this association is causal. This study aims to investigate the causal effects of sleep-related traits on MetS using Mendelian randomization (MR).

METHODS: Single-nucleotide polymorphisms strongly associated with daytime napping, insomnia, chronotype, short sleep, and long sleep were selected as genetic instruments from the corresponding genome-wide association studies (GWAS). Summary-level data for MetS were obtained from two independent GWAS datasets. Univariable and multivariable MR analyses were conducted to investigate and verify the causal effects of sleep traits on MetS.

RESULTS: The univariable MR analysis demonstrated that genetically predicted daytime napping and insomnia were associated with increased risk of MetS in both discovery dataset (OR daytime napping  = 1.630, 95% CI 1.273, 2.086; OR insomnia  = 1.155, 95% CI 1.108, 1.204) and replication dataset (OR daytime napping  = 1.325, 95% CI 1.131, 1.551; OR insomnia  = 1.072, 95% CI 1.046, 1.099). For components, daytime napping was positively associated with triglycerides (beta = 0.383, 95% CI 0.160, 0.607) and waist circumference (beta = 0.383, 95% CI 0.184, 0.583). Insomnia was positively associated with hypertension (OR = 1.101, 95% CI 1.042, 1.162) and waist circumference (beta = 0.067, 95% CI 0.031, 0.104). The multivariable MR analysis indicated that the adverse effect of daytime napping and insomnia on MetS persisted after adjusting for BMI, smoking, drinking, and another sleep trait.

CONCLUSION: Our study supported daytime napping and insomnia were potential causal factors for MetS characterized by central obesity, hypertension, or elevated triglycerides.